The Lucerne Toolbox 2 to optimise axillary management for early breast cancer: a multidisciplinary expert consensus.

Clinical axillary lymph node management in early breast cancer has evolved from being merely an aspect of surgical management and now includes the entire multidisciplinary team. The second edition of the "Lucerne Toolbox", a multidisciplinary consortium of European cancer societies and patient representatives, addresses the challenges of clinical axillary lymph node management, from diagnosis to local therapy of the axilla. Five working packages were developed, following the patients' journey and addressing specific clinical scenarios. Panellists voted on 72 statements, reaching consensus (agreement of 75% or more) in 52.8%, majority (51%-74% agreement) in 43.1%, and no decision in 4.2%. Based on the votes, targeted imaging and standardized pathology of lymph nodes should be a prerequisite to planning local and systemic therapy, axillary lymph node dissection can be replaced by sentinel lymph node biopsy ( ± targeted approaches) in a majority of scenarios; and positive patient outcomes should be driven by both low recurrence risks and low rates of lymphoedema.

Breast conservation and axillary management after primary systemic therapy in patients with early-stage breast cancer: the Lucerne toolbox.

Primary systemic therapy is increasingly used in the treatment of patients with early-stage breast cancer, but few guidelines specifically address optimal locoregional therapies. Therefore, we established an international consortium to discuss clinical evidence and to provide expert advice on technical management of patients with early-stage breast cancer. The steering committee prepared six working packages to address all major clinical questions from diagnosis to surgery. During a consensus meeting that included members from European scientific oncology societies, clinical trial groups, and patient advocates, statements were discussed and voted on. A consensus was reached in 42% of statements, a majority in 38%, and no decision in 21%. Based on these findings, the panel developed clinical guidance recommendations and a toolbox to overcome many clinical and technical requirements associated with the diagnosis, response assessment, surgical planning, and surgery of patients with early-stage breast cancer. This guidance could convince clinicians and patients of the major clinical advancements purported by primary systemic therapy, the use of less extensive and more targeted surgery to improve the lives of patients with breast cancer.

Oncoplastic Breast Consortium consensus conference on nipple-sparing mastectomy.

PURPOSE: Indications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion. METHODS: The panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative process in question development, voting, and wording of the recommendations followed the modified Delphi methodology. RESULTS: Consensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference. CONCLUSIONS: In case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest and most efficacious reconstruction techniques.

First international consensus conference on standardization of oncoplastic breast conserving surgery.

PURPOSE: To obtain consensus recommendations for the standardization of oncoplastic breast conserving surgery (OPS) from an international panel of experts in breast surgery including delegates from the German, Austrian and Swiss societies of senology. METHODS: A total of 52 questions were addressed by electronic voting. The panel's recommendations were put into context with current evidence and the report was circled in an iterative open email process until consensus was obtained. RESULTS: The panelists considered OPS safe and effective for improving aesthetic outcomes and broadening the indication for breast conserving surgery (BCS) towards larger tumors. A slim majority believed that OPS reduces the rate of positive margins; however, there was consensus that OPS is associated with an increased risk of complications compared to conventional BCS. The panel strongly endorsed patient-reported outcomes measurement, and recommended selected scales of the Breast-Q™-Breast Conserving Therapy Module for that purpose. The Clough bi-level classification was recommended for standard use in clinical practice for indicating, planning and performing OPS, and the Hoffmann classification for surgical reports and billing purposes. Mastopexy and reduction mammoplasty were the only two recognized OPS procedure categories supported by a majority of the panel. Finally, the experts unanimously supported the statement that every OPS procedure should be tailored to each individual patient. CONCLUSIONS: When implemented into clinical practice, the panel recommendations may improve safety and effectiveness of OPS. The attendees agreed that there is a need for prospective multicenter studies to optimize patient selection and for standardized criteria to qualify and accredit OPS training centers.

A time and motion study of subcutaneous versus intravenous trastuzumab in patients with HER2-positive early breast cancer.

Within PrefHer (NCT01401166), patients and healthcare professionals (HCPs) preferred subcutaneous (SC) over intravenous (IV) trastuzumab. We undertook a prospective, observational time and motion study to quantify patients' time in infusion chairs and active HCP time in PrefHer. Patients with HER2-positive early breast cancer received four adjuvant cycles of SC trastuzumab (600 mg fixed dose via SC single-use injection device [SID, Cohort 1] or SC handheld syringe [HHS, Cohort 2]) then four cycles of standard IV trastuzumab or the reverse sequence. Generic case report forms for IV and SC management, both in the treatment room and the drug preparation area, were tailored to reflect center practices. Patient chair time and active HCP time were recorded. We compared pooled Cohort 1 + 2 IV with Cohort 1 SC SID and Cohort 2 SC HHS mean times across eight countries and individually within them utilizing a random intercept generalized linear mixed-effects model. Per session, the SC SID saved a mean of 57 min of patient chair time versus IV (range across countries: 47-86; P < 0.0001); the SC HHS saved 55 min (40-81; P < 0.0001). Active HCP time was reduced by a mean of 13 min per session with the SC SID (range across countries: 4-16; P < 0.0001) and 17 min with the SC HHS (5-28; P < 0.0001) versus IV. SC trastuzumab, delivered via SID or HHS, saved patient chair and active HCP times versus IV infusion, supporting a transition to either SC method.

Quantitative volumetric breast density estimation using phase contrast mammography.

Phase contrast mammography using a grating interferometer is an emerging technology for breast imaging. It provides complementary information to the conventional absorption-based methods. Additional diagnostic values could be further obtained by retrieving quantitative information from the three physical signals (absorption, differential phase and small-angle scattering) yielded simultaneously. We report a non-parametric quantitative volumetric breast density estimation method by exploiting the ratio (dubbed the R value) of the absorption signal to the small-angle scattering signal. The R value is used to determine breast composition and the volumetric breast density (VBD) of the whole breast is obtained analytically by deducing the relationship between the R value and the pixel-wise breast density. The proposed method is tested by a phantom study and a group of 27 mastectomy samples. In the clinical evaluation, the estimated VBD values from both cranio-caudal (CC) and anterior-posterior (AP) views are compared with the ACR scores given by radiologists to the pre-surgical mammograms. The results show that the estimated VBD results using the proposed method are consistent with the pre-surgical ACR scores, indicating the effectiveness of this method in breast density estimation. A positive correlation is found between the estimated VBD and the diagnostic ACR score for both the CC view (p = 0.033) and AP view (p = 0.001). A linear regression between the results of the CC view and AP view showed a correlation coefficient γ = 0.77, which indicates the robustness of the proposed method and the quantitative character of the additional information obtained with our approach.

PET/MRI and PET/CT in advanced gynaecological tumours: initial experience and comparison.

PURPOSE: To compare the diagnostic accuracy of PET/MRI and PET/CT for staging and re-staging advanced gynaecological cancer patients as well as identify the potential benefits of each method in such a population. MATERIAL AND METHODS: Twenty-six patients with suspicious or proven advanced gynaecological cancer (12 ovarian, seven cervical, one vulvar and four endometrial tumours, one uterine metastasis, and one primary peritoneal cancer) underwent whole-body imaging with a sequential trimodality PET/CT/MR system. Images were analysed regarding primary tumour detection and delineation, loco-regional lymph node staging, and abdominal/extra-abdominal distant metastasis detection (last only by PET/CT). RESULTS: Eighteen (69.2 %) patients underwent PET/MRI for primary staging and eight patients (30.8 %) for re-staging their gynaecological malignancies. For primary tumour delineation, PET/MRI accuracy was statistically superior to PET/CT (p < 0.001). Among the different types of cancer, PET/MRI presented better tumour delineation mainly for cervical (6/7) and endometrial (2/3) cancers. PET/MRI for local evaluation as well as PET/CT for extra-abdominal metastases had therapeutic consequences in three and one patients, respectively. PET/CT detected 12 extra-abdominal distant metastases in 26 patients. CONCLUSION: PET/MRI is superior to PET/CT for primary tumour delineation. No differences were found in detection of regional lymph node involvement and abdominal metastases detection. KEY POINTS: • PET/MRI is superior to PET/CT for primary tumour delineation • PET/CT represents a reliable tool to detect extra-abdominal distant metastasis • PET/MRI might be the preferred imaging modality for staging cervical and endometrial tumours • Whole-body staging for detection and evaluation of extra-abdominal metastases is mandatory.

Non-invasive classification of microcalcifications with phase-contrast X-ray mammography.

Microcalcifications can be indicative in the diagnosis of early breast cancer. Here we report a non-invasive diagnostic method that may potentially distinguish between different types of microcalcifications using X-ray phase-contrast imaging. Our approach exploits the complementary nature of the absorption and small-angle scattering signals of microcalcifications, obtained simultaneously with an X-ray grating interferometer on a conventional X-ray tube. We demonstrate that the new approach has 100% sensitivity and specificity when applied to phantom data, and we provide evidence of the solidity of the technique by showing its discrimination power when applied to fixed biopsies, to non-fixed tissue specimens and to fresh, whole-breast samples. The proposed method might be further developed to improve early breast cancer diagnosis and has the potential to increase the diagnostic accuracy and reduce the number of uncomfortable breast biopsies, or, in case of widespread microcalcifications, to select the biopsy site before intervention.

The Central-European SentiMag study: sentinel lymph node biopsy with superparamagnetic iron oxide (SPIO) vs. radioisotope.

Sentinel lymph node biopsy (SLNB) is the standard surgical procedure for the axilla in early node-negative breast cancer. To date, the "gold standard" to localize the sentinel lymph node (SLN) is the radiotracer (99m)Tc with or without blue dye. The aim of this study was to evaluate potential equivalency of the new SentiMag(®) technique in comparison to the "gold standard". Within this prospective, multicentric and multinational non-inferiority study including 150 patients (99m)Tc was compared with the magnetic technique, using superparamagnetic iron oxide particles (SPIOs, Sienna+(®)) for localization of SLNs. The results showed a detection rate per patient of 97.3% (146/150) for (99m)Tc vs. 98.0% (147/150) for Sienna+(®) with a similar average number of removed SLNs per patient and a higher per patient malignancy detection rate for the SPIO tracer. We obtained convincing results that magnetic SLNB can be performed easily, safely and equivalently well in comparison to the radiotracer method.

A study on mastectomy samples to evaluate breast imaging quality and potential clinical relevance of differential phase contrast mammography.

OBJECTIVES: Differential phase contrast and scattering-based x-ray mammography has the potential to provide additional and complementary clinically relevant information compared with absorption-based mammography. The purpose of our study was to provide a first statistical evaluation of the imaging capabilities of the new technique compared with digital absorption mammography. MATERIALS AND METHODS: We investigated non-fixed mastectomy samples of 33 patients with invasive breast cancer, using grating-based differential phase contrast mammography (mammoDPC) with a conventional, low-brilliance x-ray tube. We simultaneously recorded absorption, differential phase contrast, and small-angle scattering signals that were combined into novel high-frequency-enhanced images with a dedicated image fusion algorithm. Six international, expert breast radiologists evaluated clinical digital and experimental mammograms in a 2-part blinded, prospective independent reader study. The results were statistically analyzed in terms of image quality and clinical relevance. RESULTS: The results of the comparison of mammoDPC with clinical digital mammography revealed the general quality of the images to be significantly superior (P < 0.001); sharpness, lesion delineation, as well as the general visibility of calcifications to be significantly more assessable (P < 0.001); and delineation of anatomic components of the specimens (surface structures) to be significantly sharper (P < 0.001). Spiculations were significantly better identified, and the overall clinically relevant information provided by mammoDPC was judged to be superior (P < 0.001). CONCLUSIONS: Our results demonstrate that complementary information provided by phase and scattering enhanced mammograms obtained with the mammoDPC approach deliver images of generally superior quality. This technique has the potential to improve radiological breast diagnostics.

Should less motion sensitive T2-weighted BLADE TSE replace Cartesian TSE for female pelvic MRI?

OBJECTIVES: To prospectively compare the diagnostic performance of a non-Cartesian k-space sampling T2-weighted TSE BLADE sequence with a conventional T2-weighted TSE sequence in female pelvic organs. METHODS: Forty-seven patients with sonographically indeterminate adnexal masses or uterine lesions underwent sagittal BLADE and conventional TSE at 1.5 T after glucagon administration. Two radiologists independently determined their preferred sequence by rating: overall image diagnostic quality, conspicuity of the zonal anatomy and delineation of pathologies of the uterus and cervix, presence of artefacts, and of fluid in the pouch of Douglas (Wilcoxon signed rank test). Signal-to noise ratios (SNRs) and contrast-to-noise ratios (CNRs) were measured for the myometrium versus the rectus abdominis muscle (Student's t-test). RESULTS: BLADE significantly (p < 0.0001) reduced motion and ghosting artefacts and showed improved conspicuity (p = 0.3/0.24), but overall image quality did not differ significantly (inter-observer agreement BLADE κ = 0.89; TSE κ = 0.84). In the majority of cases (53.2 % vs 59.6 %, respectively, κ = 0.82) radiologists preferred conventional TSE due to better image contrast (p < 0.0001) and visibility of free pelvic fluid (p ≤ 0.0001). SNR (TSE 57.5 ± 37.7; BLADE 16.6 ± 12.2) and CNR (TSE 40.4 ± 33.5; BLADE 7.2 ± 8.8) were significantly higher on conventional TSE (p < 0.0001). CONCLUSIONS: Although BLADE reduces motion artefacts and provides a clearer delineation of uterine zonal anatomy compared with conventional TSE, this comes at the expense of overall contrast. MAIN MESSAGES: • Use of BLADE may reduce T2 contrast and thus visibility of free pelvic fluid or cystic structures • Non-Cartesian sampling of k-space such as BLADE is beneficial due to less motion sensitivity • BLADE provides clearer delineation and conspicuity of uterine zonal anatomy on pelvic MRIs.

Breast Abscesses: Diagnosis, Treatment and Outcome.

BACKGROUND: The aim of our study was to analyze diagnostic results, different treatment modalities, and the outcome of patients with breast abscesses treated at our institution in a multi-modality breast team, to determine whether minimally invasive treatments are successful. METHODS: 110 patients with mastitis and suspected breast abscesses at our institution between January 2000 and end of September 2007 were retrospectively analyzed. Abscesses were diagnosed using ultrasonography (US), and the material obtained using US-guided fine needle aspiration (FNA) was further examined. RESULTS: 29% of the patients were treated conservatively with antibiotics only, 51% were treated with US-guided FNA or drainage placement. 11% of the patients underwent additional surgery after minimally invasive treatment (i.e. conversion rate). 9% of the patients underwent primary surgery. Early complications occurred in 7% of patients treated minimally invasive but not in patients treated with surgery alone. Late complications occurred in 5% of patients who underwent minimally invasive treatments and in 30% of patients who underwent surgery. CONCLUSIONS: US-guided FNA as a minimally invasive therapy in combination with antibiotics was found to successfully treat most breast abscesses and, in cases where a larger volume of pus was involved, the placement of an additional drainage catheter was effective.

MRI of the female pelvis: a possible pitfall in the differentiation of haemorrhagic vs. fatty lesions using fat saturated sequences with inversion recovery.

The use of fat-saturated techniques should be an integral part of the work-up of any T1-hyperintense structure in the female pelvis for tissue characterization and for differentiation of a fat-containing ovarian mature teratoma from a haemorrhagic lesion. Two cases with haematocolpos and haematometra are presented, respectively. The haemorrhagic content showed high signal both on T1- and T2-weighted images, whereas an unexpected signal decrease in the fat-saturated T2-weighted inversion-recovery sequence was encountered. This unspecific suppression of signal in tissues with similar T1 relaxation times as fat can lead to a diagnostic pitfall both in T1- and T2-weighted STIR pulse sequences. Furthermore, a loss of signal on T2-weighting may also be due to the phenomenon of "T2-shading" in T1-bright ovarian endometrioma. Therefore, the fat-specific spectral fat-saturation of T1-weighted images is strongly recommended for tissue characterization in gynaecological disease.

The first analysis and clinical evaluation of native breast tissue using differential phase-contrast mammography.

OBJECTIVES: Phase-contrast and scattering-based x-ray imaging are known to provide additional and complementary information to conventional, absorption-based methods, and therefore have the potential to play a crucial role in medical diagnostics. We report on the first mammographic investigation of 5 native, that is, freshly dissected, breasts carried out with a grating interferometer and a conventional x-ray tube source. Four patients in this study had histopathologically proven invasive breast cancer. One male patient, without the presence of any malignant formations within the resected breast, was included as a control specimen. MATERIALS AND METHODS: We used a Talbot-Lau grating setup installed on a conventional, low-brilliance x-ray source; the interferometer operated at the fifth Talbot distance, at a tube voltage of 40 kVp with mean energy of 28 keV, and at a current of 25 mA. The device simultaneously recorded absorption, differential phase and small-angle scattering signals from the native breast tissue. These quantities were then combined into novel color- and high-frequency-enhanced radiographic images. Presurgical images (conventional mammography, ultrasonography, and magnetic resonance imaging) supported the findings and clinical relevance was verified. RESULTS: Our approach yields complementary and otherwise inaccessible information on the electron density distribution and the small-angle scattering power of the sample at the microscopic scale. This information can be used to potentially answer clinically relevant, yet unresolved questions such as unequivocally discerning between malignant and premalignant changes and postoperative scars and distinguishing cancer-invaded regions within healthy tissue. CONCLUSIONS: We present the first ex vivo images of fresh, native breast tissue obtained from mastectomy specimens using grating interferometry. This technique yields improved diagnostic capabilities when compared with conventional mammography, especially when discerning the type of malignant conversions and their breadth within normal breast tissue. These promising results advance us toward the ultimate goal, using grating interferometry in vivo on humans in a clinical setting.

Indeterminate adnexal masses at ultrasound: effect of MRI imaging findings on diagnostic thinking and therapeutic decisions.

OBJECTIVE: To determine the impact of MRI including DWI on therapeutic decision-making and costs in the work-up of patients with a indeterminate adnexal mass on ultrasound. METHODS: Thirty-eight patients with indeterminate ovarian lesions scheduled for surgery were included in this prospective study. In a questionnaire, the surgeon characterised the lesions based on a morphological score and determined the surgical procedure. The assessment was re-evaluated knowing MR findings and correlated with the final diagnosis. A cost-benefit analysis of MRI was performed. The impact of including DWI in the MR protocol was assessed. RESULTS: MRI provided major diagnostic information in 11/38 cases (28.9%) resulting in abstention from surgery in 5 cases; moderate additional information was recorded in 10/38 (26.3%) patients. Overall a net cost saving (3'676 EUR) was achieved. DWI did not show a significant difference between benign and malignant lesions. Teratomas yielded significantly lower mean ADC values (0.597 × 10(-3) mm(2)/s) compared with all other adnexal lesions (1.812 × 10(-3) mm(2)/s); the mean ADC values in endometrioma (1.387 × 10(-3) mm(2)/s) were significantly lower than in other cystic lesions (2.372 × 10(-3) mm(2)/s). CONCLUSION: Inclusion of MRI in the diagnostic algorithm of the indeterminate adnexal mass allows better differentiation of ovarian lesions resulting in a change of therapeutic decision-making with net cost savings.

Successful remission of extensive liver metastases in a breast cancer patient with acute liver failure using a combined chemotherapy regimen with mitomycin, folinate, and 5-fluorouracil (Mi/Fo/FU).

BACKGROUND: Liver failure due to disseminated hepatic secondaries represents a therapeutic dilemma in patients with metastatic breast cancer (MBC). Reduced liver function and non-assessable toxicity are limiting factors in the selection of chemotherapeutic agents. Currently, there is no standard treatment after failure of anthracycline-and taxane-based first-line therapies, although there is a variety of well evaluated drugs such as capecitabine. CASE REPORT: We report on a 45-year-old breast cancer patient with disseminated hepatic metastases. She presented in markedly poor condition, showing substantial ascites and extensive jaundice. Blood chemistry analysis showed increased serum levels of liver enzymes (aspartate aminotransferase 271 U/l, alanine transaminase 101 U/l), bilirubin (7.9 mg/dl), and CA 15-3 (1,459 U/l). We induced a palliative chemotherapy with mitomycin, folinate, and 5-fluorouracil (Mi/Fo/FU). The patient improved impressively after the first cycle of systemic therapy. Liver enzymes stabilized continuously, CA 15-3 returned to normal. The patient was discharged 2 weeks after the treatment start. Chemotherapy was well tolerated under dose escalation, no grade 3/4 toxicity was observed. The progression-free interval was 5 months. CONCLUSIONS: A combination therapy with Mi/Fo/FU appears to be a reasonable and tolerable alternative salvage strategy for patients with liver failure due to hepatic breast cancer metastases.

Safe total intrafascial laparoscopic (TAIL) hysterectomy: a prospective cohort study.

This study directly compares total intrafascial laparoscopic (TAIL) hysterectomy with vaginal (VH) and abdominal (AH) hysterectomy with regard to safety, operating time and time of convalescence. The study is a prospective cohort study (Canadian Task Force classification II-2), including data from patients of a single university-affiliated teaching institution, admitted between 1997 and 2008 for hysterectomy due to benign uterus pathology. Patient data were collected pre-, intra- and postoperatively and complications documented using a standardised data sheet of a Swiss obstetric and gynaecological study group (Arbeitsgemeinschaft Schweizerische Frauenkliniken, Amlikon/Switzerland). Classification of complications (major complications and minor complications) for all three operation techniques, evaluation of surgeons and comparison of operation times and days of hospitalisation were analysed. 3066 patients were included in this study. 993 patients underwent AH, 642 VH and 1,431 total intrafascial hysterectomy. No statistically significant difference for the operation times comparing the three groups can be demonstrated. The mean hospital stay in the TAIL hysterectomy, VH and AH groups is 5.8 +/- 2.4, 8.8 +/- 4.0 and 10.4 +/- 3.9 days, respectively. The postoperative minor complications including infection rates are low in the TAIL hysterectomy group (3.8%) when compared with either the AH group (15.3%) or the VH group (11.2%), respectively. The total of minor complications is statistically significant lower for TAIL hysterectomy as for AH (O.R. 4.52, CI 3.25-6.31) or VH (O.R. 3.16, CI 2.16-4.62). Major haemorrhage with consecutive reoperation is observed statistically significantly more frequent in the AH group when compared to the TAIL hysterectomy group, with an O.R. of 6.13 (CI 3.05-12.62). Overall, major intra- and postoperative complications occur significant more frequently in the AH group (8.6%) when compared to the VH group (3%) and the TAIL hysterectomy group (1.8%). The incidence of major complications applying the standardised TAIL hysterectomy technique is not related to the experience of the surgeons. We conclude that a standardised intrafascial technique of total laparoscopic (TAIL) hysterectomy using an anatomically developed special uterine device is associated with a very low incidence of minor and major intra- and postoperative complications. The direct comparison of complication rates with either vaginal or abdominal hysterectomy favours the total laparoscopic technique, and therefore, this technique can be recommended as a relatively atraumatic procedure. The operation times are comparable for all three techniques without any statistically significant differences. This technique for laparoscopic hysterectomy is shown to be equally safe when applied by experienced gynaecologic surgeons or by residents in training. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10397-010-0569-0) contains supplementary material, which is available to authorized users.